Two enzymes involved in isoprenoid metabolism of the sagebrush Artemisia tridentata spiciformis, chrysanthemyl diphosphate synthase (CDS) and farnesyl diphosphate synthase (FDS) have recently been cloned and over-expressed in Escherichia coli. Each enzyme represents a class of enzymes that promote the condensation of five carbon isoprenes. The proposed mechanism and products produced by the two enzymes are distinct; however, the amino acid sequences are 69% identical. The high sequence homology of these two enzymes provides a unique opportunity to investigate the structural basis for the different mechanisms catalyzed by each enzyme. A strategy of domain swapping will be employed to map the regions of the enzymes responsible for the unique chemistry catalyzed by CDS and FDS. The high sequence homology of these two enzymes provides a unique opportunity to investigate the structural basis for the different mechanisms catalyzed by each enzyme. A strategy of domain swapping will be employed to map the regions of the enzymes responsible for the unique chemistry catalyzed by CDS and FDS. Understanding the determinants that differentiate these two fundamental mechanisms in isoprenoid metabolism that are believed to use similar mechanisms. An example of squalene synthase (SQS), an enzyme linked to arteriosclerosis. SQS forms the intermediate presqualene diphosphate by a mechanism that is identical to that proposed for CDS to form chrysanthemyl diphosphate. By catalyzing the first committed step of the de novo biosynthesis of cholesterol, SQS, is a main target for drugs aimed at lowering serum cholesterol.